The invention relates to the 9-deazaguanine derivatives, namely 2-amino-7-(1-substituted-2-hydroxyethyl)-3,5-dihydro-pyrrolo[3,2-d] pyrimidin-4-ones as defined herein which are particularly potent purine nucleoside phosphorylase (PNP) inhibitors, methods for preparation thereof, pharmaceutical compositions comprising said compounds, and a method of inhibiting purine nucleoside phosphorylase and of treating conditions in mammals which are responsive to purine nucleoside phosphorylase inhibition using said compounds or pharmaceutical compositions comprising said compounds of the invention.
7-(1-Substituted-hydroxyalkyl)-3,5-dihydropyrrolo[3,2-d]pyrimidin-4-ones, including specific 7-(1-aryl-3-hydroxypropyl)-substituted compounds, are, inter alia, disclosed in U.S. Pat. No. 5,189,139 and International Application WO 93/21187. However, there is no suggestion to prepare the novel 7-(1-substituted-2-hydroxyethyl)-substituted compounds of the present invention to obtain unexpectedly potent PNP inhibitors.
The compounds of the invention are particularly useful in mammals as purine nucleoside phosphorylase (PNP) inihibitors, as selective inhibitors of T-cell formation and thus function as immunosuppressants suppressing cellular immunity. They can be used for the prevention and treatment of transplant rejection and for treatment of autoimmune diseases such as rheumatoid arthritis, psoriasis and dermatitis, Crohn's disease, uveitis, asthma, and diabetes in mammals. They can also be used to potentiate the antiviral and antitumor effect of antiviral or antitumor purine nucleosides, in particular 2',3'-dideoxypurine nucleosides for the treatment of retrovirus infections such as AIDS (acquired immunodeficiency syndrome); and also for the treatment of gout.